The structure, function and utilization of eukaryotic promoter sequences required for the specific initiation of RNA transcription are being studied. The endogenous retrovirus CPC-1 isolated from Colobus polykomos kidney cells has proven to be a unique probe for the modulators of eukaryotic gene expression. Specific goals are: (1) to elucidate the specific DNA signal sequences (promoters) which control efficient transcription; (2) to evaluate the evolutionary fate of retroviral sequences; and (3) to develop efficient eukaryotic cloning vectors. The CPC-1 long terminal repeat (LTR) has been sequenced and shown to contain two overlapping promoters. Comparison of these sequences with those of transcriptionally inactive parent proviruses shows that the promoter initiation domain covers at least 10 nucleotides (-32 to -23. The active promoter has been subcloned and used to express a truncated tk gene ligated into the viral cap site. Data suggest that amplification of endogenous proviral sequences has been the result of gene transposition. A DNA sequence in sheep related to the CPC-1 promoter has been found to be responsible for the insertional activation of bovine leukemia virus.